PMID- 11112152 OWN - NLM STAT- MEDLINE DCOM- 20010126 LR - 20171116 IS - 1073-449X (Print) IS - 1073-449X (Linking) VI - 162 IP - 6 DP - 2000 Dec TI - Halothane reduces the early lipopolysaccharide-induced lung inflammation in mechanically ventilated rats. PG - 2278-86 AB - Several studies suggest that anesthetics modulate the immune response. The aim of this study was to investigate the effect of halothane and thiopental on the lung inflammatory response. Rats submitted or not to intratracheal (IT) instillation of lipopolysaccharides (LPS) were anesthetized with either halothane (0. 5, 1, or 1.5%) or thiopental (60 mg. kg(-1)) and mechanically ventilated for 4 h. Control rats were treated or not by LPS without anesthesia. Lung inflammation was assessed by total and differential cell counts in bronchoalveolar lavage fluids (BALF) and by cytokine measurements (tumor necrosis factor-alpha [TNF-alpha], interleukin-6 [IL-6], macrophage inflammatory protein-2 [MIP-2], and monocyte chemoattractant protein-1 [MCP-1]) in BALF and lung homogenates. In the absence of LPS treatment, neither halothane nor thiopental modified the moderate inflammatory response induced by tracheotomy or mechanical ventilation. Cell recruitment and cytokine concentrations were increased in all groups receiving IT LPS. However, in halothane-anesthetized rats (halothane > or = 1%), but not in thiopental-anesthetized rats, the LPS-induced lung inflammation was altered in a dose-dependent manner. Indeed, when using 1% halothane, polymorphonuclear leukocyte (PMN) recruitment was decreased by 55% (p < 0.001) and TNF-alpha, IL-6, and MIP-2 concentrations in BALF and lung homogenates were decreased by more than 60% (p < 0.001) whereas total protein and MCP-1 concentrations remained unchanged. The decrease of MIP-2 (observed at the protein and messenger RNA [mRNA] level) was strongly correlated to the decrease of PMN recruitment (r = 0.73, p < 0.05). This halothane-reduced lung inflammatory response was transient and was reversed 20 h after the end of the anesthesia. Our study shows that halothane > or = 1%, delivered during 4 h by mechanical ventilation, but not mechanical ventilation per se, alters the early LPS-induced lung inflammation in the rat, suggesting a specific effect of halothane on this response. FAU - Giraud, O AU - Giraud O AD - Unite INSERM 408, Faculte de Medecine Xavier Bichat, Paris, France. FAU - Seince, P F AU - Seince PF FAU - Rolland, C AU - Rolland C FAU - Lecon-Malas, V AU - Lecon-Malas V FAU - Desmonts, J M AU - Desmonts JM FAU - Aubier, M AU - Aubier M FAU - Dehoux, M AU - Dehoux M LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Respir Crit Care Med JT - American journal of respiratory and critical care medicine JID - 9421642 RN - 0 (Anesthetics, Inhalation) RN - 0 (Anesthetics, Intravenous) RN - 0 (Lipopolysaccharides) RN - JI8Z5M7NA3 (Thiopental) RN - UQT9G45D1P (Halothane) SB - IM MH - Anesthetics, Inhalation/administration & dosage/*pharmacology MH - Anesthetics, Intravenous/administration & dosage/pharmacology MH - Animals MH - Base Sequence MH - Bronchoalveolar Lavage Fluid/chemistry/cytology MH - Escherichia coli MH - Halothane/administration & dosage/*pharmacology MH - Lipopolysaccharides MH - Lung/chemistry/drug effects/pathology MH - Male MH - Molecular Sequence Data MH - Pneumonia/chemically induced/*metabolism/pathology MH - Polymerase Chain Reaction/methods/statistics & numerical data MH - Rats MH - Rats, Sprague-Dawley MH - *Respiration, Artificial MH - Specific Pathogen-Free Organisms MH - Thiopental/administration & dosage/pharmacology MH - Time Factors EDAT- 2000/12/09 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/12/09 11:00 PHST- 2000/12/09 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/12/09 11:00 [entrez] AID - 10.1164/ajrccm.162.6.9807113 [doi] PST - ppublish SO - Am J Respir Crit Care Med. 2000 Dec;162(6):2278-86. doi: 10.1164/ajrccm.162.6.9807113.